Certain compounds are known in the art for their ability to provide enhanced permeability of skin or other body surfaces to biologically active agents. However, when these permeation enhancers are hydrophobic, their true permeation enhancement effect is often not completely expressed in practical application due to their limited solubility in water. The low solubility leads to a slow dissolution rate of the permeation enhancers in the water. Since partitioning of the permeation enhancers into the skin is much controlled by the dissolution, it is a slow process and there can be a significant lag time between application and attainment of the desired active agent flux.
The problem with hydrophobic permeation enhancers can be solved by co-delivering a hydrophobic enhancer with a solvent carrier such as propylene glycol, ethanol, isopropyl alcohol or other small molecules which can solubilize the hydrophobic enhancers. However, with such solvents, irritation problems to the host are frequently encountered.
Therefore, despite the development of the art, there has remained a continuing need for improved techniques in the transdermal delivery of active agents with hydrophobic permeation enhancers.